A major component of drug abuse research involves identifying the various biological, pharmacological and environmental factors that contribute to differences in drug sensitivity across subject populations. The existing literature describes numerous examples of these differences and several contributing variables have been identified. One set of factors that exerts a strong influence on sensitivity to the effects of addictive drugs is the social and environmental history of the subject. In our original AREA application, we proposed a series of studies examining whether social and environmental enrichment influences sensitivity to the antinociceptive and rewarding effects of [unreadable] opioids in male rats. Those studies have been completed, and in this application we report that enriched rats are more sensitive than isolated rats to the effects of [unreadable] opioids, and that these effects are most apparent when lower efficacy opioids are tested. These findings suggest that the [unreadable] opioid receptor system is sensitive to social and environmental manipulations, and that these manipulations have functional consequences for sensitivity to the effects of [unreadable] opioid agonists. In this competitive renewal, we propose to examine the effects of social and environmental manipulations on sensitivity to opioids and cocaine in two animal models of drug-seeking behavior, the conditioned place preference procedure and the drug self-administration procedure. As a novel line of investigation, we plan to examine the effects of social and environmental enrichment in both male and female subjects, and to determine whether gonadal hormones influence these effects. Finally, we also propose a novel line of studies examining the effects of aerobic exercise on drug-seeking behavior, determining whether gonadal hormones influence these effects in male and female subjects. These studies should identify the critical biological, pharmacological and environmental factors contributing to differences in drug-seeking behavior across subject populations. [unreadable] [unreadable] [unreadable]